Mortality in Appalachia has consistently risen over the past fifteen years, in contrast to decreasing mortality rates observed for the remainder of the U.S. Rural populations are consistently underrepresented in clinical trials, and few comprehensive data resources exist to support studies of health and correlates of adverse health outcomes. Clinical and Translation (C/T) research focused on the health issues confronting poor rural populations is critical to addressing and remediating WV's significant health disparities. While building on the considerable achievements in Years 1-5 of three distinct cores (i.e. Ethics & Regulatory Knowledge, Biomedical Informatics Resources, and Clinical Trials Research Unit), the proposed new core, Clinical Research Resources and Facilities (CRRF), has been specifically designed to address the limitations of recruiting rural participants into clinical trials and to support new analyses of relevant clinical databases. In addition, CRRF addresses the need for more efficient and timely processes for supporting clinical research. The overall goals of the CRRF core are to create clinical research infrastructures to translate basic research to clinical practice, assuring West Virginians access to cutting edge clinical trials and providing answers to research questions relevant to the health of rural communities. These overall goals will be accomplished by expanding research partnerships to support continued development and implementation of innovative approaches to understand and improve the health of WV through realization of the following specific aims: 1) create a Clinical Trials Center of Excellence (CTCOE) with connection to rural communities and practitioners, thereby providing access to cutting-edge trials addressing health disparities affecting West Virginians, 2) leverage the Integrated Data Repository (IDR2), containing clinical data on 2 million persons, and partnership through the Appalachian Research Consortium to facilitate outcomes research, predictive modeling, and geospatial analysis, and 3) establish the Environmental Exposures Unit to stimulate environmental health research in collaboration with the National Institute for Occupational Safety and Health (NIOSH). Achievement of Aim 1 will result in facilities to conduct Phase 1-4 trials while Aim 2 will provide access to clinical information from not only the 2 million WV patients in IDR2, but to clinical data from the Universities of Kentucky and Cincinnati. Truly innovative is the availability of an urban comparator, accomplished by connection to clinical data from Mount Sinai Medical Center in New York City. Finally, Aim 3 leverages NIOSH expertise to examine the health impact of energy extraction methods. Environmental exposure studies will be enhanced by the availability of geospatial coding of IDR2 data.